Different clinical trials in Down syndrome (DS) have failed to demonstrate efficacy of novel drugs developed to improve cognitive function. The lack of standardized and adapted evaluation tools is one of the reasons for these failures.1
Furthermore, though there are specific cognitive screening tests for individuals with DS, no regulatory accepted international tools have been developed to assess cognitive impairment or quality of life able to detect the potential clinical efficacy of a new drug.
Most of the preclinical benchmark tests analyze long term memory and spatial orientation. Unfortunately, these cognitive functions are largely preserved in individuals with DS, in which the major cognitive impairment involves working memory and memory flexibility.
ICOD will use the NIH Toolbox Cognitive Battery, validated for several intellectual disabilities including DS composed of seven tests analyzing different cognitive abilities and provides several composite scores.
The clinical efficacy of AEF0217 in rescuing the deficits of working memory and memory flexibility will be assessed with the NIH Toolbox Cognitive Battery, that has been specifically validated in for several intellectual disabilities including DS. The NIH Toolbox is composed of seven tests analyzing different cognitive abilities and provides several composite scores.
The fluid cognition composite score is validated1,2 as the most adapted to evaluate the cognitive deficit in Down syndrome patients and was chosen as the primary efficacy endpoint in the Phase II clinical trial with AEF0217 planned to be performed in the ICOD program.
The fluid cognition composite score derives from the scores of five tests assessing the following cognitive domains:
- Attention: Flanker inhibitory control and visual attention.
- Episodic memory: Picture sequence memory test.
- Working memory: List sorting working memory test.
- Cognitive flexibility: Dimensional change card sort (DCCS) test.
- Processing speed: Pattern comparison processing speed test.
The use of NIH Toolbox Cognitive Battery for Intellectual Disabilities represent an innovative psychometric approach to demonstrate the clinical efficacy of AEF0217.
1. Hessl D, et al. The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions. J Neurodev Disord. 2016 ;8(1):35;
2. Shields RH, et al. Validation of the NIH Toolbox Cognitive Battery in intellectual disability. Neurology. 2020 Feb 24. pii: 10.1212/WNL.0000000000009131